Morinda officinalis How (MO), a member of the Rubiaceae family, is a small vine that grows widely in tropical and subtropical regions. The roots of this plant (named Bajitian) have been recorded in the pharmacopeia of the People's Republic of China (2010 edition) to help strengthen the bones and kidneys and to enhance the immune system function. In contrast to Western countries, in eastern Asia, particularly in China, herbal therapies have been common throughout centuries. The roots of Morinda officinalis continue to be traditionally used to treat rheumatoid arthritis, diabetes and hypertension in North East Asia (Choi, J. et al., 2005). This plant has also been used to treat impotence, menstrual disorders, and other inflammatory diseases such as dermatitis. Compositions including components derived from many plants, including Radix Morindae Officinalis, have been disclosed as agents for the treatment of cancer and other disorders of the prostate and (U.S. Pat. No. 7,223,424 to Wen Hsien Chou).
A number of constituents have been isolated from Morinda officinalis. These include iridoid glycosides, anthraquinones, and oligosaccharides. The pharmacological effects of some of these constituents have been identified. Iridoids are a class of secondary metabolites found in a wide variety of plants and in some animals (U.S. Patent Application No. 20110217394). Iridoids were found to possess a wide range of bioactivities, including anti-inflammatory (Shin et al., 2013) and antinoiceptive activities. Several anthraquinones have also been shown to have anti-osteoporotic activity.
The flavonoid biosynthetic pathway is well established and has been widely studied in a number of different plant species (see, for example, Koes et al., Trends in Plant Sciences, 10(5):236-242(2005)). Chalcone synthase (E.C, 2.3.1.74) is the first enzyme in the flavonoid-specific branch of the phenylpropanoid biosynthetic pathway (Dixon et al., Plant Cell7:1085-1097 (1995)). As such it is a key enzyme in secondary metabolism (U.S. Pat. No. 7,202,397).
MO has a 5-7 year growth cycle. Years 1-5 is the growth phase and years 6-7 is the harvest phase. Due to the high medicinal value of its secondary metabolites, MO has been exhaustively excavated in the wild. These secondary metabolites are not essential for plant growth and hence are produced in small amounts (Zhou et. al., 2011). Thus, high numbers of plants are needed for therapeutic amounts, which intensify the foraging and subsequent depletion of wild plants. There is an urgent need to create alternative sources of these metabolites to support patient needs.
Inflammatory bowel disease (IBD) is a type of autoimmune disease in which the body's own immune system attacks elements of the digestive system. One IBD subtype, ulcerative colitis (UC), is an idiopathic chronic relapsing-remitting inflammatory disorder that affects the colon, characterized by diarrhea and rectal bleeding. Current drug treatment for UC patients includes 5 aminosalicyclic acid (5-ASA), corticosteroids, thiopurines, and anti-TNF antibodies. These agents aim to control the extent of inflammation by immunosuppression. However, long-term efficacy is achieved only in approximately one-third of the patients with moderate to severe disease and is frequently accompanied by adverse effects such as risks of infections, lymphoma, and skin cancer.